The synthesis and reactions of β-substituted ethyl sulfates

The synthesis of β-substituted ethyl sulfates and their reactions with nucleophilic reagents has been studied. Amines, phenolates, carboxylates, amine oxides, carbanions, and thiophenolates reacted with ethylene sulfate in high yield, with short reaction times, and at low temperatures, to form β-substituted ethyl sulfates. The β-substituted ethyl sulfates were easily hydrolyzed and in some cases were converted into polymeric material.     

A method of synthesis of phosphinic acids on the basis of hypophosphites: VII. Synthesis of pseudo-γ-aminobutanoyl peptides and other phosphinic analogs of γ-aminobutyric acid

A method of synthesis of pseudo-γ-aminobutanoyl peptides and other phosphinic analogs of γ-aminobutyric acid from hypophosphites is suggested. Silyl phosphonites formed by in situ addition of bis-(trimethylsilyl) hypophosphite to the corresponding α-substituted acrylates, styrene, or vinyl phosphonate used as unsaturated components in the synthesis react in situ with N-(ω-bromoalkyl)phthalimides by an Arbuzov reaction scheme, affording ω-(phthalimido)alkylphosphinic acids possessing β-substituted β-(alkoxycarbonyl)ethyl, β-phenylethyl, or β-(diethoxyphosphinoyl)ethyl substituents. Acid hydrolysis of these reaction products gives the target aminophosphinic acids: phosphinic analogs of γ-aminobutyric acid.     

Bis-β-sulfanylethylester and cyclic disulfide-S-oxides as precursors of bifunctionalized anionic derivatives with two oxidized sulfurs

The cyclic disulfide and the bis-β-sulfanyl ethyl ester derived from dithiol, N,N′-1,2-phenylenebis(3-methyl-3-sulfanylbutanamide) were used as precursors to prepare upon oxidation the cyclic disulfide-S-oxides and the thioether sulfur oxidized species including thioether/sulfoxide, bis-sulfoxide, sulfoxide/sulfone, and bis-sulfone. Ring cleavage with KOH/EtOH of the cyclic disulfide-S-monooxide followed by reaction of the opened intermediate with ethyl acrylate afforded the sulfinate/β-sulfanyl ethyl ester derivative. Selective oxidation with 1 and 2 equiv of (3S)-3-tert-butyl-3-methyl-2-(phenylsulfonyl)oxaziridine or with 3 equiv of DMD led to the isolation of a series of compounds containing a sulfonate and a β-sulfanyl, a β-sulfinyl, and a β-sulfonyl ethyl ester. Retro-Michaël reaction applied to the β-sulfonyl/β-sulfinyl and bis-β-sulfonyl derivatives enabled to produce compounds containing a sulfinate and a β-sulfinyl or a β-sulfonyl ethyl ester as well as the bis-sulfinate dianion. DMD oxidation of the latter afforded the bis-sulfonate dianion. All these anionic species were characterized by ¹H NMR, mass spectrometry, HRMS or elemental analysis. Sulfenates in such pseudopeptidic structures could not be isolated from the ring cleavage of the cyclic disulfide-S-dioxide or from a retro-Michaël reaction applied to the β-sulfinyl ethyl ester. A cyclization reaction leading to an isothiazolidin-3-one is likely to occur as observed from the ring cleavage of the cyclic disulfide-S-dioxide. Finally, Ni(II) and Co(III) have been inserted into the disulfinate dianion leading to the corresponding diamidato/disulfinato complexes S-bonded to Ni(II) or Co(III) centers.     

Synthesis of nucleobase-functionalized β-peptoids and β-peptoid hybrids

The solid-phase synthesis of a new class of nucleobase-modified peptide-mimetic oligomers is described. β-Peptoids and β-peptoid hybrids bearing thymine on the side chain are prepared from N-Fmoc-N-[2-(thymin-1-yl)ethyl]-β-alanine.     

Syntheses of polyfluoro-α-amino acids

Some fluorine-containing amino acids have been known to inactivate certain enzymes selectively and irreversibly. We have synthesized β-(polyfluoro ethyl)alanines and β-(trifluorovinyl)alanine from polyfluoroiodoethanes and acrylate.The synthetic schemes of β-(polyfluoroethyl)- alanines are shown below.

Using similar procedures, we have also prepared β-(polyfluoroethyl)-β-methylalanines, CF₂XCFX′CH(CH₃)- CH(NH₂)CO₂H from polyfluoroiodoethanes and ethyl crotonate.β-(Trifluorovinyl)alanine was synthesized in a good yield from the ester of β-(dichlorotrifluoro ethyl)alanine as follows:

The reactive trifluorovinyl group in the amino acid allows us to synthesize various kinds of fluorine- containing amino acids with a functional group through radical and ionic addition reactions. Some reactions of the ester of N-acetylated β-(trifluorovinyl)alanine with alkoxides (nucleophilic addition) and alcohols (radical addition) will be mentioned.

     

Chemical composition, anti-inflammatory, molluscicidal and free-radical scavenging activities of the leaves of Ficus radicans 'Variegata' (Moraceae)

The methanol crude extract of the leaves of Ficus radicans Roxb. 'Variegata' (Moraceae) and the n-hexane, ethyl acetate and aqueous methanol fractions resulting from its fractionation were evaluated for their anti-inflammatory, molluscicidal and free-radical scavenging activities. The crude extract and fractions exhibited significant inhibition of inflammation in both croton oil (CO)-induced ear oedema in mice (p<0.001) and carrageenan-induced rat paw oedema models (p<0.01). The molluscicidal assay against Biomphalaria glabrata showed a weak activity for the n-hexane fraction (DL(50)=?400 μg mL(-1)). A moderated 1,1-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity was observed for the ethyl acetate fraction (IC(50)=?66.2 μg mL(-1)). Fractionation of the extracts through chromatographic methods afforded the coumarins 7-methoxycoumarin, 7-hydroxy-6-methoxycoumarin and methoxy-3,4-dihydrocoumarin, the steroids β-sitosterol and β-sitosterol 3-O-β-glucopyranoside, as well as a cinnamic acid derivative and a flavonoid identified as trans-4-methoxy-2-β-D-glucopyranosyloxy cinnamic acid and quercetin 3-O-β-D-xylopyranosyl-(1?→?2)-α-L-rhamnopyranoside, respectively. The compounds were identified on the basis of their NMR spectral data and comparison with those previously reported in the literature.     

Solution polymerization of vinyl monomers in the presence of poly(N-acetyliminoethylene) macroazoinitiators

New block copolymers with poly(N-acetyliminoethylene) and vinyl sequences were obtained by a two-step synthetic approach. In the first stage macroinitiators of poly(N-acetyliminoethylene) type, with azo groups inserted in the main chain, were prepared. They were latter used in the radical polymerization of some vinyl monomers [styrene, methacrylic acid, methyl methacrylate, butyl methacrylate, β-(N-carbazolyl)ethyl acrylate, β-(methacryloyfoxy)ethyl 3,5-dinitrobenzoate]. The resulting block copolymers were characterized by spectral methods, elemental analysis, gel permeation chromatography, and electron microscopy. The kinetic study of the thermal and photochemical decomposition of the synthesized macroazoinitiators, as well as the polymerization data, suggest a dependence of their initiating efficiency on the length of the poly(N-acetyliminoethylene) segments. © 1994 John Wiley & Sons, Inc.     

Synthesis and spectral data of some heterocyclic compounds. The reaction of arylpropiolic esters with tetralones and acetylcyclopropane

Reaction of phenylpropiolic ester (I) with α- and β-tetralones in the presence of sodium ethoxide yielded 5,6-dihydro-7,8-benzflavones and ethyl β-(2-tetralon-1-yl)cinnamates, as a result of Claisen and Michael reactions, respectively. The reaction of I with 3-ethoxy-2-cyclohexen-l-one and acetylcyclopropane in the presence of sodium ethoxide yielded acetylenic β-diketones and 2-aryl-6-cyclopropylpyran-4-ones, respectively. These products were identified on the basis of spectral and analytical data.     

2,4-Disubstituted Pyrrolo[2,3-d]pyrimidine α-D- and β-D-Ribofuranosides Related to 7-Deazaguanosine

Nucleobase-anion glycosylation (KOH, tris[2-(2-methoxyethoxy)ethyl]amine (TDA-1), MeCN) of the pyrrolo[2,3-d]pyrimidines 4a – d with 5-O-[(1,1-dimethylethyl)dimethylsilyl]-2,3-O-(1-methylethylidene)-α-D -ribo-furanosyl chloride ( 5 ) gave the protected β-D -nucleosides 6a – d stereoselectively (Scheme 1). Contrary, the β-D -halogenose 8 yielded the corresponding α-D -nucleosides ( 9a and 9b ) apart from minor amounts of the β-D -anomers. The deprotected nucleosides 10a and 11a were converted into 4-substituted 2-aminopyrrolo[2,3-d]-pyrimidine β-D -ribofuranosides 1 . 10c , 12 , 14 , and 16 and into their α-D -anomers, respectively (Scheme 2). From the reaction of 4b with 5 , the glycosylation product 7 was isolated, containing two nucleobase moieties.     

DBU-catalyzed condensation of acyldiazomethanes to aldehydes in water and a new approach to ethyl β-hydroxy α-arylacrylates

DBU-catalyzed condensation of ethyl diazoacetate (EDA) with aldehydes in pure water afforded corresponding β-hydroxy α-diazo carbonyl compounds. The β-hydroxy group of the products was further converted into β-siloxy group. The Rh(II)-catalyzed reaction of the β-aryl β-siloxy α-diazo carbonyl compounds gave 1,2-aryl shift products predominantly. The three-step transformation constitutes an efficient synthesis of ethyl β-hydroxy α-arylacrylates.     

Preparation of 3,5-diethoxycarbonyl-2,6-dimethyl-1,4-dihydro-isonicotinic acid and 3,5-diacetyl-2,6-dimethyl-1,4-dihydroisoni-cotinic acid and their salts

The reaction of glyoxylic acid with ethyl β-aminocrotonate or acetyl-acetone imine has given the corresponding derivatives of 1, 4-dihydro-isonicotinic acid and their water-soluble salts.     

β-Benzotriazolylethyl phosphates and phosphonic esters

β-(1-Benzotriazolyl)ethyl dibutyl phosphate and the 2-benzotriazolyl analog were prepared from dibutyl phosphite and 1- and 2-(β-hydroxyethyl)benzotriazoles, respectively. Dialkyl β-(N-benzotriazolyl) ethylphosphonates were prepared from the corresponding dialkyl β-bromoethylphosphonates. In both types of compounds, elimination of benzotriazole occurs in base; interestingly, such elimination is significantly faster in each series for the 2-substituted benzotriazole than for the corresponding 1-isomer.     

多元酚的氰乙基和乙氧羰乙基化 I.

In the presence of alkoxide, resorcinol, methyl and nitro substituted resorcinol give C-polycyanoethyl-substituted products. When the 2-, 4- and 6-positions were occupied the O-cyanoethylation could occur. In the reaction of 2-nitroresorcinol with ethyl acrylate two β-carbethoxyethyl groups are introduced in a similar way to the 4-and 6-positions. The carbethoxyethylation products of resorcinol and 2-methylresorcinol lose ethyl alcohol during distillation giving the corresponding lactones.     

Heterocyclizations of Di- and Tricarbonyl Indole Derivatives. Synthesis of β-Carbolines, 3H-[1,2,5]Triazepino-[5,4-a]indol-4(5H)-one,and 5,10-Dihydro[1,2]diazepino-[4,5-b]indol-4(3H)-one

Russian Journal of Organic Chemistry - A synthetic approach to β-carbolines has been proposed on the basis of heterocyclization of ethyl 2-(2-benzoyl-1H-indol-3-yl)acetate with...     

Synthesis of highly cytotoxic tiazofurin mimics bearing a 2,3-anhydro function in the furanose ring

This paper describes a divergent de novo synthesis of 2-(2,3-anhydro-β-d-ribofuranosyl)thiazole-4-carboxamide (2′,3′-anhydro-tiazofurin) and the corresponding α- and β-homo-C-nucleosides. The synthetic approach was based on a multistep transformation of d-glucose into suitably protected aldonthioamides followed by their subsequent cyclocondensation with ethyl bromopyruvate to form the thiazole ring. Antiproliferative activity of the target molecules is reported against several human tumour cell lines.     

Uncatalyzed reactions of α-(trihaloethylidene)nitroalkanes with push-pull enamines: a new type of ring-ring tautomerism in cyclobutane derivatives and the dramatic effect of the trihalomethyl group on the reaction pathway

A new type of ring-ring isomerism, which consists of the reversible transformation of cyclobutane derivatives into substituted 1,2-oxazine N-oxides was found and studied by NMR spectroscopy and X-ray diffraction analysis. The starting materials were prepared by the stereoselective reaction of α-(trifluoroethylidene)nitroalkanes, which react with ethyl β-morpholino- and β-piperidinocrotonates at the more nucleophilic α-position, whereas the reaction of α-(trichloroethylidene)nitroalkanes proceeds at the β-methyl group to give the corresponding linear products.     

The reaction of substituted ethylα-bromocinnamates with tetrabutyl ammonium fluoride

The reaction of ethyl α-bromocinnamates with tetrabutyl ammonium fluoride(TBAF) was influenced largely by the position of the substituent at the phenyl ring.While the substrates without an ortho substituent at the phenyl ring were transformed to the corresponding β-fluoro ethyl cinnamates under the reaction conditions,the presence of an ortho substituent only resulted in the formation of ethyl 3-phenylpropiolate derivatives.The reaction of ethyl 2-bromo-3-(4-methoxyphenyl) acrylate also failed to deliver the hydrofluorination product due to the electron-donating effect of the methoxy group.     

Optical resolution of mandelic acid derivatives by column chromatography on crosslinked cyclodextrin gels

Crosslinked α- and β-cyclodextrin gels (α-CD-E and β-CD-E) were used for the chromatographic resolution of racemic mandelic acid and its derivatives. β-CD-E bound L -(+)-isomers preferentially over D -(?)-isomers and resolved DL -methyl mandelate to give a D -(?)-isomer of 100% optical purity in the first fraction. Mandelic acid, ethyl mandelate, and O-methylated mandelic acid yielded resolutions of 65–83% in initial fractions. α-CD-E, on the contrary, bound D -(?)-isomers more strongly than L -(+)-isomers, resolving DL -methyl mandelate to a smaller extent than β-CD-E. Binding of DL -mandelic acid and DL -methyl mandelate on β-CD-E was studied quantitatively by the equilibrium method. β-CD-E has a similar binding capacity to starch with 1:1 stoichiometry but bound much more strongly than starch. β-CD-E has the same mode of selectivity as starch for the asymmetric binding of the mandelic acid derivatives, but α-CD-E has a reverse selectivity to β-CD-E and starch.     

Cross metathesis of β-carotene with electron-deficient dienes. A direct route to retinoids

Cross metathesis (CM) reactions of β-carotene and alkenes occur regioselectively in the presence of the Hoveyda second generation catalyst. Scission of the C15-C15′ and C11-C12 bonds of β-carotene in all CM reactions predominates. The reaction with ethyl (2E,4E/Z)-3-methylhexa-2,4-dienoate is both regio- and diastereoselective, and affords ethyl all-trans-retinoate as the major product, if suitable CM conditions are applied.     

Synthesis of methyl(ethyl) pyrazolo[4,3-b]pyridine-6-carboxylates and their conversion to tert-butyl 4,5,6,7-tetrahydropyrazolo-[4,3-b]pyridine-6-carboxylates

Chemistry of Heterocyclic Compounds - N-Boc-4-aminopyrazole-5-carbaldehydes react with methyl 3,3-dimethoxypropanoate or β-keto esters in acetic acid under reflux to form methyl(ethyl)...